Vγ9Vδ2 T cells (Vγ9Vδ2 T lymphocyte) are spotlighted as cells capable of performing tumor cell elimination and intracellular defense against parasitic bacteria and parasites without being restricted by major histocompatibility antigens. Cancer treatment with use of Vγ9Vδ2 T cells obtained from human peripheral blood is currently under research. However, a limited quantity of Vγ9Vδ2 T cells present in human peripheral blood makes it difficult to obtain a sufficient amount of Vγ9Vδ2 T cells for use in immunotherapy.
A recent report demonstrated that bisphosphonates, which are used, for example, for osteoporosis treatment, exhibit antitumor action by acting directly on cancer cells, and also act on γδ T cells to encourage growth and activation of γδ T cells (Blood, 97:2917-2918, 2001). γδ T cells thus proliferated have a strong antitumor cell activity. Many studies have been conducted to establish therapies in which γδ T cells separated from blood of a cancer patient's own are proliferated in vitro using a bisphosphonate, and the lymphocytes thus obtained are returned to the body. Some studies reported promising results (Curr. Med. Chem., 15:1147-1153, 2008). In addition, there is disclosed a method (see Japanese Patent No. 4025019; registered on Oct. 12, 2007) in which the proliferation of Vγ2Vδ2 T cells is carried out with addition of an organic pyrophosphate derivative and use of interleukin 2 (hereinafter abbreviated as “IL-2”) as a cofactor. There is also disclosed another method (see Int. J. Cancer 116, 94-99, 2005) in which the proliferation of Vγ9Vδ2 T cells is carried out with addition of zoledronate and use of IL-2 as a cofactor.
However, such conventional arts have a problem in that Vγ9Vδ2 T cells cannot be proliferated sufficiently. For example, with the addition of zoledronate and IL-2, proliferation gain of Vγ9Vδ2 T cell can be improved only up to about 800 fold maximally (Int. J. Cancer 116, 94-99, 2005). With such a low proliferation gain, this method requires a large number of Vγ9Vδ2 T cells to be proliferated. This necessitates collecting a large amount of peripheral blood from the patient, thereby giving the patient much pain and burden.
Under such circumstances, an art is long awaited that enables more efficient proliferation of Vγ9Vδ2 T cells for establishment of a cancer treatment using Vγ9Vδ2 T cells.